GSBS Dissertations and Theses

Approval Date

7-15-2014

Document Type

Doctoral Dissertation

Academic Program

Neuroscience

Department

Department of Neurobiology; Francis Lab

First Thesis Advisor

Michael M. Francis

Keywords

Axons, Caenorhabditis elegans, Motor Neurons, Neurobiology, Neurons, Synapses

Subjects

Dissertations, UMMS; Axons; Caenorhabditis elegans; Motor Neurons; Neurobiology; Neurons; Synapses

Abstract

Activity plays diverse roles in shaping neuronal development and function. These roles range from aiding in synaptic refinement to triggering cell death during traumatic brain injury. Though the importance of activity-dependent mechanisms is widely recognized, the genetic underpinnings of these processes have not been fully described. In this thesis, I use the motor circuit of Caenorhabditis elegans as a model system to explore the functional and morphological consequences of modulating neuronal activity.

First, I used a gain-of-function ionotropic receptor to hyperactivate motor neurons and asked how increased excitation affects neuronal function. Through this work, I identified a cell death pathway triggered by excess activation of motor neurons. I also showed that suppression of cell body death failed to block motor axon destabilization, providing evidence that death of the cell body and of motor axons can be genetically separated.

Secondly, I removed excitatory drive from a simple neural circuit and asked how loss of excitatory activity alters circuit development and function. I identified excitatory motor neurons as master regulators of inhibitory synaptic connectivity. Additionally, I was able to identify previously undescribed activity-dependent mechanisms for regulating inhibitory synapses in both developing and mature neural circuits.

Finally, I show data to implicate the highly conserved genes neurexin and neuroligin in determining inhibitory synapse connectivity. Collectively this work has lent insight into activity-dependent mechanisms in place to regulate neuronal development and function, a core function of neurobiology that is relevant to the study of a wide range of neurological disorders.

DOI

10.13028/M2JW2T

Rights and Permissions

Copyright is held by the author, with all rights reserved.

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